EP1241941A2 - Pesticidal activity of functionalized alkenes - Google Patents
Pesticidal activity of functionalized alkenesInfo
- Publication number
- EP1241941A2 EP1241941A2 EP00980451A EP00980451A EP1241941A2 EP 1241941 A2 EP1241941 A2 EP 1241941A2 EP 00980451 A EP00980451 A EP 00980451A EP 00980451 A EP00980451 A EP 00980451A EP 1241941 A2 EP1241941 A2 EP 1241941A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- enoate
- enoic acid
- hept
- group
- phenylhept
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5082—Supracellular entities, e.g. tissue, organisms
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/10—Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
- A01N37/38—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/26—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
- C07C57/42—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
- C07C57/60—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/608—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a ring other than a six-membered aromatic ring in the acid moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C07C69/618—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety having unsaturation outside the six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- the present invention concerns functionalized alkenes, along with alkane and alkyne analogs thereof, that have pesticidal activity, along with methods of use thereof.
- mosquitoes for example, transmit diseases caused by viruses, and many are vectors for disease-causing nematodes and protozoa.
- Mosquitoes of the genus Anopheles transmit Plasmodium, the protozoan which causes malaria, a devastating disease which results in approximately 1 million deaths annually.
- the mosquito species Aedes aegypti transmits an arbovirus that causes yellow fever in humans.
- arboviruses transmitted by Aedes species include the causative agents of dengue fever, eastern and western encephalitis, Venezuelan equine encephalitis, St. Louis encephalitis, chikungunya, oroponehe and bunyarnidera.
- the genus Culex which includes the common house mosquito C. pipiens, is implicated in the transmission of various forms of encephalitis and filarial worms.
- the common house mosquito also transmits Wuchereria banuffi and Brugia malayi, which cause various forms of lymphatic filariasis, including elephantiasis. Trypanasomas cruzi, the causative agent of Chagas' disease, is transmitted by various species of blood- ingesting Triatominae bugs.
- the tsetse fly (Glossina spp.) transmits African trypanosomal diseases of humans and cattle. Many other diseases are transmitted by various blood-ingesting pest species.
- the order Diptera contains a large number of blood-ingesting and disease-bearing insects, including, for example, mosquitoes, black flies, no-see-ums (punkies), horse flies, deer flies and tsetse flies.
- Various pesticides have been employed in efforts to control or eradicate populations of disease-bearing pests, such as disease-bearing blood-ingesting pests.
- DDT a chlorinated hydrocarbon, has been used in attempts to eradicate malaria-bearing mosquitoes throughout the world.
- chlorinated hydrocarbons examples include BHC, lindane, chlorobenzilate, methoxychlor, and the cyclodienes (e.g., aldrin, dieldrin, chlordane, heptachlor, and endrin).
- cyclodienes e.g., aldrin, dieldrin, chlordane, heptachlor, and endrin.
- Organophosphates Another common class of pesticides is the organophosphates, which is perhaps the largest and most versatile class of pesticides.
- Organophosphates include, for example, parathion, Malathion, diazinon, naled, methyl parathion, and dichlorvos.
- Organophosphates are generally much more toxic than the chlorinated hydrocarbons. Their pesticidal effect results from their ability to inhibit the enzyme cholinesterase, an essential enzyme in the functioning of the insect nervous system. However, they also have toxic effects on many animals, including humans.
- the carbamates a relatively new group of pesticides, include such compounds as carbamyl, methomyl, and carbofuran. These compounds are rapidly detoxified and eliminated from animal tissues. Their toxicity is thought to involve a mechanism similar to the mechanism of the organophosphates; consequently, they exhibit similar shortcomings, including animal toxicity.
- a major problem in pest control results from the capability of many species to develop pesticide resistance. Resistance results from the selection of naturally- occurring mutants possessing biochemical, physiological or behavioristic factors that enable the pests to tolerate the pesticide. Species of Anopheles mosquitoes, for example, have been known to develop resistance to DDT and dieldrin. DDT substitutes, such as MalathionTM, propoxur and fenitrothion are available; however, the cost of these substitutes is much greater than the cost of DDT.
- TTLE trypsin and trypsin-like enzymes
- Aedes aegypti an early trypsin that is found in the midgut of newly emerged females is replaced, following the blood meal, by a late trypsin .
- a female mosquito typically weighs about 2 mg and produces 4 to 6 ug of trypsin within several hours after ingesting a blood meal.
- TMOF Trypsin Modulating Oostatic Factor
- Borovsky purified an oostatic hormone 7,000-fold and disclosed that injection of a hormone preparation into the body cavity of blood imbibed mosquitoes caused inhibition of egg development and sterility (Borovsky, D. [1985] Arch, insect Biochem. Physiol. 2:333-349). Following these observations, Borovsky (Borovsky, D. [1988] Arch. Ins. Biochem. Physiol. 7:187-210) reported that injection or passage of a peptide hormone preparation into mosquitoes inhibited the TTLE biosynthesis in the epithelial cells of the gut. This inhibition caused inefficient digestion of the blood meal and a reduction in the availability of essential amino acids translocated by the hemolymph, resulting in arrested egg development in the treated insect.
- Borovsky observed that this inhibition of egg development does not occur when the oostatic hormone peptides are inside the lumen of the gut or other parts of the digestive system (Borovsky, D. [1988], supra).
- the isolated hormone, (a ten amino acid peptide) and two TMOF analogues were disclosed in U.S. Patent Nos. 5,011,909 and 5,130,253, and in a 1990 publication (Borovsky et al. [1990] FASEB J. 4:3015- 3020).
- U.S. Patent No. 5,358,934 discloses truncated forms of the full length TMOF which have prolines removed from the carboxy terminus, including the peptides YDP AP, YDPAPP, YDPAPPP, and YDP APPPP.
- TMOF analogs that have been identified to date are primarily peptide analogs. In order to provide a greater diversity of new pesticidal compounds, it would be desirable to possess compounds that are TMOF analogues, yet are not peptides.
- the present invention is based on the discovery of non-peptide organic compounds that have a structure analogous to or reminiscent of the TMOF structure and have pesticidal activity.
- the present invention concerns pesticidal compounds that inhibit digestion in pests by terminating or otherwise blocking synthesis of digestive enzymes by activating a TMOF receptor (collectively referred to herein as "pesticidal compounds").
- the pesticidal compounds and other compounds of the present invention are usefully employed in the control of pests, particularly insect pests such as mosquitoes, which ingest blood.
- a first aspect of the present invention is a method of controlling a pest such as an insect pest, comprising administering to said pest a pesticidally effective amount of a non-peptide TMOF analog (that is, an organic compound that has TMOF activity).
- a pesticidally effective amount of a non-peptide TMOF analog that is, an organic compound that has TMOF activity.
- This definition is specifically intended to exclude the peptide TMOF agonists or analogs disclosed in, inter alia, U.S. Patents Nos. 5,011,909; 5,130,253; and 5,358,934, the disclosures of which are incorporated by reference herein in their entirety.
- Particular pesticidal compounds/non-peptide TMOF analogs of the present invention have the formula I below:
- X is selected from the group consisting of -CHCH-, -CH CH 2 -, and -CC-;
- Z is selected from the group consisting of -OH, -NH and -OR 6 wherein R 6 is loweralkyl; n and m are each at least 1 and together total an integer from 2, 3 or 4 to 6, 8, 10 or 12; and Ri, R 2 , R , R , and R 5 are each independently selected from the group consisting of -H, -OH, halo, loweralkyl, and loweralkoxy; subject to the proviso that: and Ri, R and R 3 , or R 3 and R 4 on the phenyl ring may together represent to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and R ⁇ 0 are each independently selected from the group consisting of -H, -OH, halo, loweralkyl, and loweralkoxy.
- a second aspect of the present invention is a method of initiating a TMOF receptor-mediated biological response.
- the method comprises contacting to a TMOF receptor in vivo or in vitro for a time and in an amount sufficient to initiate a TMOF receptor-mediated biological response a compound of Formula I as described herein.
- the biological response may be any suitable biological response mediated by the
- TMOF receptor including but not limited to inhibition of biosynthesis of a digestive enzyme such as trypsin.
- the subject compounds can also be used to control pests of agricultural crops, for example by applying the compounds to the agricultural crops.
- pests include, for example, coleopterans (beetles), lepidopterans (caterpillars), and mites.
- the compounds of the subject invention can also be used to control household pests including, but not limited to, ants and cockroaches.
- Another aspect of the subject invention pertains to a method for controlling pests, particularly insect pests, comprising administering to said pest a pesticidally effective amount of a pesticidal compound of the subject invention.
- the subject invention provides pest control compositions comprising pesticidal compounds and a suitable pesticidal carrier.
- the pest control compositions are formulated for application to the target pests or their situs.
- the methods and materials of the subject invention provide a novel approach to controlling insects and insect-transmitted diseases.
- the compounds of the subject invention have advantageous activity and increased resistance to proteolysis over previously disclosed compounds.
- the term "pesticidally effective" is used to indicate an amount or concentration of a pesticidal compound which is sufficient to reduce the number of pests in a geographical locus as compared to a corresponding geographical locus in the absence of the amount or concentration of the pesticidal compound.
- the term “pesticidal” is not intended to refer only to the ability to kill pests, such as insect pests, but also includes the ability to interfere with a pest's life cycle in any way that results in an overall reduction in the pest population.
- the term “pesticidal” includes inhibition of a pest from progressing from one form to a more mature form, e.g., transition between various larval instars or transition from larva to pupa or pupa to adult.
- the term “pesticidal” is intended to encompass anti-pest activity during all phases of a pest's life cycle; thus, for example, the term includes larvacidal, ovicidal, and adulticidal activity.
- loweralkyl as used herein means Ci to C 4 alkyl, preferably methyl, ethyl or propyl.
- loweralkoxy as used herein means C] to C alkoxy, preferably methoxy, ethoxy, or propoxy.
- halo as used herein means halogen, preferably fluoro, chloro, bromo or iodo, most preferably fluoro.
- X is selected from the group consisting of-CHCH-, -CH CH 2 -, and -CC-;
- Z is selected from the group consisting of -OH, -NH 2 and -OR 6 wherein R 6 is loweralkyl; n and m are each at least 1 and together total an integer from 2, 3 or 4 to 6, 8, 10 or 12; and R), R 2 , R 3 , R , and R 5 are each independently selected from the group consisting of -H, -OH, halo, loweralkyl, and loweralkoxy; subject to the proviso that: a pair of Ri and R l s R 2 and R 3 , R3 and R 4 , or R and R 5 on the phenyl ring may together represent to form with the phenyl ring illustrated above a naphthyl ring system, wherein R 7 , R 8 , R 9 , and Rio are each independently selected from the group consisting of -H, -OH, halo, loweralkyl, and loweralkoxy.
- the phenyl ring and the carbonyl carbon may be either cis (Z) or trans (E) with respect to one another.
- the trans configuration is prefe ⁇ ed.
- Methyl E-7-phenylhept-4-enoate which has the structure:
- E-10-phenyldec-6-enoic acid which has the structure:
- Additional examples of acids of the present invention include:
- E-7-(4-hydroxyphenyl)hept-4-enoic acid E-7-(2,4-dibromophenyl)hept-4-enoic acid; E-7-(4-methylphenyl)hept-4-enoic acid; E-7-(2,4-diethylphenyl)hept-4-enoic acid; E-7-(2-ethoxyphenyl)hept-4-enoic acid; E-7-(2,4,-dipropoxyphenyl)hept-4-enoic acid: and E-10-(2,4-difluorophenyl)dec-4-enoic acid.
- amides of the present invention include: E-7-(2,4-difluorophenyl)hept-4-enoic acid amide; E-7-(4-methoxyphenyl)hept-4-enoic acid amide; E- 10-phenyldec-6-enoic acid amide;
- E-7-(2,4-difluorophenyl)dec-6-enoic acid amide E-7-(4-methoxyphenyl)dec-6-enoic acid amide
- Z-7-phenylhept-4-enoic acid amide E-7-(2,4-difluorophenyl)dec-6-enoic acid amide
- E-7-(4-methoxyphenyl)dec-6-enoic acid amide E-7-(4-methoxyphenyl)dec-6-enoic acid amide
- Z-7-phenylhept-4-enoic acid amide Z-7-phenylhept-4-enoic acid amide.
- esters of the present invention include: Methyl E-7-(2,4-difluorophenyl)hept-4-enoate; Methyl E-7-(4-methoxyphenyl)hept-4-enoate; Methyl E-10-phenyldec-6-enoate; Methyl E-7-(2,4-difluorophenyl)dec-6-enoate;
- the double bond can be replaced with a single bond to produce an analogous series of active compounds that are alkanes.
- the double bond can be replaced with a triple bond to produce an analogous series of active compounds that are alkynes.
- the phenyl ring can be replaced with a naphthyl ring to produce an analogous series of active compounds based upon a naphthyl ring system.
- Compounds of the present invention can be made by the technique described in M. Ansell and J. Ducker, Reduced cyclic Compounds. Part XL The Cyclisation of ⁇ -Arylalkenoic Acids, J. Chem. Soc. 206-212 (1961), or variations thereof that will be apparent to those skilled in the art.
- a further aspect of the subject invention are addition salts, complexes, or prodrugs such as esters of the compounds described herein, especially the nontoxic pharmaceutically or agriculturally acceptable acid addition salts.
- the acid addition salts can be prepared using standard procedures in a suitable solvent from the parent compound and an excess of an acid, such as hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, maleic, succinic, ethanedisulfonic or methanesulfonic acids. Esterification to form derivatives such as the methyl or ethyl esters, can also be performed using standard procedures. Tartarate salts can be prepared in accordance with standard procedures. Also, derivation of the pesticidal compounds with long chain hydrocarbons will facilitate passage through the cuticle into the pest body cavity. Therefore, in a further embodiment, the subject invention provides compositions comprising the pesticidal compounds bound to lipids or other carriers.
- an acid such as hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, maleic, succinic, ethanedisulfonic or methanesulfonic acids. Esterification to form derivatives such as the methyl or ethyl esters
- the subject invention concerns novel pest control compounds and methods for using such compounds.
- the subject compounds have an LD 50 against mosquito larvae of less than 3.0 ⁇ mole/ml. More preferably, the compounds have an LD 50 of less than 2.0 ⁇ mole/ml, and, most preferably, the compounds have an LD 50 of less than 1.0 ⁇ mole/ml.
- LD 50 refers to a lethal dose of a peptide able to cause 50% mortality of larvae maintained on a diet of 1 mg/ml autoclaved yeast supplemented with the pesticidal polypeptide.
- Control of pests using the pest control compounds of the subject invention can be accomplished by a variety of methods known to those skilled in the art.
- the plant pests that can be controlled by the compounds of the subject invention include pests belonging to the orders Coleoptera, Lepidopterans, Hemiptera and Thysanoptera. These pests all belong to the phylum Arthropod.
- Other pests that can be controlled according to the subject invention include members of the orders Diptera, Siphonaptera, Hymenoptera and Phthiraptera.
- Other pests that can be controlled by the compounds of the subject invention include those in the family Arachnida, such as ticks, mites and spiders.
- the compounds of the subject invention to control pests can be accomplished readily by those skilled in the art having the benefit of the instant disclosure.
- the compounds may be encapsulated, incorporated in a granular form, solubilized in water or other appropriate solvent, powdered, and included into any appropriate formulation for direct application to the pest or to a pest inhabited locus.
- Formulated bait granules containing an attractant and the pesticidal compounds of the present invention can be applied to a pest-inhabited locus, such as to the soil.
- Formulated product can also be applied as a seed-coating or root treatment or total plant treatment at later stages of the crop cycle.
- Plant and soil treatments may be employed as wettable powders, granules or dusts, by mixing with various inert materials, such as inorganic minerals (phyllosilicates, carbonates, sulfates, phosphates, and the like) or botanical materials (powdered corncobs, rice hulls, walnut shells, and the like).
- the formulations may include spreader-sticker adjuvants, stabilizing agents, other pesticidal additives, or surfactants.
- Liquid formulations may be aqueous-based or non-aqueous (i.e., organic solvents), or combinations thereof, and may be employed as foams, gels, suspensions, emulsions, microemulsions or emulsifiable concentrates or the like.
- the ingredients may include rheological agents, surfactants, emulsifiers, dispersants or polymers.
- the pesticidal concentration will vary widely depending upon the nature of the particular formulation, particularly whether it is a concentrate or to be used directly.
- the pesticidal compound will be present in the composition by at least about 0.0001% by weight and may be 99 or 100% by weight of the total composition.
- the pesticidal carrier may be from 0.1% to 99.9999%) by weight of the total composition.
- the dry formulations will have from about 0.0001-95% by weight of the pesticide while the liquid formulations will generally be from about 0.0001-60% by weight of the solids in the liquid phase. These formulations will be administered at about 50 mg (liquid or dry) to 1 kg or more per hectare.
- the formulations can be applied to the pest or the environment of the pest, e.g., soil and foliage, by spraying, dusting, sprinkling or the like.
- the pest control compounds may also be provided in tablets, pellets, briquettes, bricks, blocks and the like which are formulated to float, maintain a specified depth or sink as desired.
- the formulations, according to the present invention are formulated to float on the surface of an aqueous medium; in another embodiment they are formulated to maintain a depth of 0 to 2 feet in an aqueous medium; in yet another embodiment the formulations are formulated to sink in an aqueous environment.
- Methods of identifying a non-peptide TMOF agonist from a peptide TMOF agonist are a further aspect of the present invention. Such methods typically comprise the steps of: modeling in a computer (preferably with simulated annealing) a model peptide TMOF agonist selected from the group consisting of TMOF and peptide
- TMOF analogs determining in said computer spatial orientations for at least one key feature of said model peptide compound; generating in said computer a putative non-peptide TMOF agonist structure, said structure including (t) said at least one key feature and (it) spatial orientations for said at least one key feature co ⁇ esponding to said spatial orientations for said at least one key feature of said model peptide compound; then synthesizing said putative non-peptide TMOF agonist; and then screening said putative non-peptide TMOF agonist to determine the presence of TMOF activity therein.
- Peptide TMOF agonists or analogs that may be used as a basis for modeling of the instant invention include but are not limited to those disclosed in, inter aha, U.S.
- TMOF and other TMOF peptide agonists preferably tripeptide fragments of
- TMOF may be modeled by the INSIGHTTM software (available through the North
- compounds produced by the method that have TMOF agonist activity and can be used in the methods described herein generally have the structure P-R-C, where P is a phenyl group, R is an alkane, alkene, or alkyne, and C is a carboxylate group, all of which may be substituted or unsubstituted.
- P is a phenyl group
- R is an alkane, alkene, or alkyne
- C is a carboxylate group, all of which may be substituted or unsubstituted.
- E-7-Phenylhept-4-enoic acid was prepared from commercially available dihydrocinnamaldehyde in five steps. Dihydrocinnamaldehyde was combined with the lithium salt of ethyl diethoxyphosphonioacetate in tetrahydrofuran at room temperature. The resulting unsaturated ester, ethyl 5-phenylpent-2-enoate, was purified by chromatography. The unsaturated ester was then reduced to the allylic alcohol, E-5-phenylpent-2-en-l-ol, by reaction with excess diisobutylaluminum hydride in tetrahydrofuran at -78° C.
- the purified alcohol was then converted to the bromide, E-l-bromo-5-phenylpent-2-ene, by reaction with triphenylphosphine and carbon tetrabromide in methyl ene chloride at 0° C.
- the purified bromide was then used to alkylate the sodium salt of di ethyl malonate to provide the diester, methyl E- l-carbomethoxy-5-phenylhept-4-enoate.
- the diester was purified by chromatography and then subjected to saponification using methanolic sodium hydroxide.
- the diacid was purified by acid/base extraction and then used directly in the next step of the reaction sequence.
- Decarboxylation was effected by heating the neat diacid at 170° C (under Ar) for 30 minutes.
- the product, E-7-phenylhept-4-enoic acid was obtained in greater than 95% purity. Any residual diacid was removed by dissolving the acid in hexane and filtering. All compounds in the reaction sequence were fully characterized by spectral analysis (infrared and nuclear magnetic spectroscopy) and new compounds were analyzed by combustion analysis.
- EXAMPLE 2 7-Phenylheptanoic Acid 7-Phenylheptanoic acid was prepared from E-7-phenylhept-4-enoic acid by hydrogenation at 40 psi using 5% palladium on carbon as the catalyst. Quantitative conversion of the alkene to the alkane was observed by thin layer chromatographic analysis. The product acid was purified by chromatography on silica gel and fully characterized by spectroscopic methods (infrared and nuclear magnetic resonance) and combustion analysis.
- E-7-(4-Methoxyphenyl)hept-4-enoic acid was prepared in the same fashion as E-7-phenylhept-4-enoic acid by substituting 3-(4-methoxyphenyl) propional for dihydrocinnamaldehyde as the starting material in the synthetic sequence.
- 3-(4-methoxyphenyl)propional was combined with the lithium salt of ethyl diethoxyphosphonioacetate in tetrahydrofuran at room temperature.
- the resulting unsaturated ester, ethyl 5-(4-methoxyphenyl)pent-2-enoate was purified by chromatography.
- the unsaturated ester was then reduced with excess diisobutylaluminum hydride in tetrahydrofuran at -78°C.
- the purified alcohol was then converted to the bromide, E-l-bromo-5-(4-methoxyphenyl)pent-2-ene, by reaction with triphenylphosphine and carbon tetrabromide in methylene chloride at 0°C.
- the purified bromide was then used to alkylate the sodium salt of diethyl malonate to provide the diester, methyl E-l-carbomethoxy-5-(4-methoxyphenyl)hept- 4-enoate.
- the diester was purified by chromatography and then subjected to saponification using methanolic sodium hydroxide.
- the diacid was purified by acid/base extraction and then used directly in the next step of the reaction sequence. Heating the neat diacid at 170°C (under Ar) for 30 minutes effected decarboxylation. The product, E-7-(4-methoxyphenyl)hept-4-enoic acid, was obtained in greater than 95% purity. Any residual diacid was removed by dissolving the acid in hexane and filtering. All compounds in the reaction sequence were fully characterized by spectral analysis and new compounds were analyzed by combustion analysis.
- E-7-(4-hydroxyphenyl)hept-4-enoic acid was prepared from E-7-(4- methoxyphenyl)hept-4-enoic acid by removal of the methyl ether with boron tribromide. Boron tribromide was added to a solution of E-7-(4-methoxyphenyl)hept- 4-enoic acid in methylene chloride at -78°C and sti ⁇ ed for four hours. The product, E-7-(4-hydroxyphenyl)hept-4-enoic acid, was obtained by aqueous work-up of the reaction mixture followed by chromatography on silica gel, and was fully characterized by spectroscopic methods (infrared and nuclear magnetic resonance) and combustion analysis.
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Abstract
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/457,509 US6521664B1 (en) | 1999-12-08 | 1999-12-08 | Pesticidal activity of functionalized alkenes |
US457509 | 1999-12-08 | ||
PCT/US2000/031558 WO2001041543A2 (en) | 1999-12-08 | 2000-11-16 | Pesticidal activity of functionalized alkenes |
Publications (2)
Publication Number | Publication Date |
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EP1241941A2 true EP1241941A2 (en) | 2002-09-25 |
EP1241941B1 EP1241941B1 (en) | 2003-06-18 |
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ID=23817017
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP00980451A Expired - Lifetime EP1241941B1 (en) | 1999-12-08 | 2000-11-16 | Pesticidal activity of functionalized alkenes |
Country Status (8)
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---|---|
US (1) | US6521664B1 (en) |
EP (1) | EP1241941B1 (en) |
JP (1) | JP2004508276A (en) |
AT (1) | ATE242964T1 (en) |
AU (1) | AU1771001A (en) |
CA (1) | CA2393207A1 (en) |
DE (1) | DE60003466D1 (en) |
WO (1) | WO2001041543A2 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US6660770B2 (en) * | 1999-12-08 | 2003-12-09 | North Carolina State University | Pesticidal activity of functionalized alkenes |
US6720450B2 (en) | 2001-12-13 | 2004-04-13 | North Carolina State University | Pesticidal activity of functionalized cyclopropanes |
CZ2010996A3 (en) * | 2010-12-30 | 2012-04-11 | Zentiva, K.S. | Process for preparing O-substituted (2R,3R)-3-(3-hydroxyphenyl)-2-methyl-4-pentenoic acids |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
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GB2005271A (en) | 1977-10-05 | 1979-04-19 | May & Baker Ltd | Ethylene derivatives |
US4204071A (en) | 1978-05-04 | 1980-05-20 | Zoecon Corporation | 4-Aryl-3-butenoic acids and lower alkyl esters |
US4880624A (en) * | 1988-03-18 | 1989-11-14 | The Board Of Trustees Of The University Of Illinois | Volatile attractants for diabrotica species |
US4897397A (en) | 1988-12-16 | 1990-01-30 | Schering Corporation | Aryl-alkynoic, alkenoic or alkanoic compounds and compositions useful as antiallergy and anti-inflammatory agents |
US5130253A (en) | 1989-04-07 | 1992-07-14 | University Of Florida | DNAs Encoding mosquito oostatic hormones |
US5011909A (en) | 1989-04-07 | 1991-04-30 | University Of Florida | Novel compositions and process for inhibiting digestion in blood-sucking insects |
JPH07103001B2 (en) | 1989-10-19 | 1995-11-08 | 高砂香料工業株式会社 | Acaricide |
US5386507A (en) | 1991-07-18 | 1995-01-31 | Teig; Steven L. | Computer graphics system for selectively modelling molecules and investigating the chemical and physical properties thereof |
ATE184882T1 (en) | 1992-12-11 | 1999-10-15 | Univ Florida | MATERIALS AND METHODS FOR PEST CONTROL |
US5747537A (en) | 1995-09-05 | 1998-05-05 | Washington University | Method of inhibiting parasitic activity |
AR035621A1 (en) | 1998-09-29 | 2004-06-23 | Univ Florida | TMOF RECEIVER, ISOLATED POLINUCLEOTIDE, COMPOUND, METHOD FOR CONTROLLING A PEST, METHOD FOR IDENTIFYING INSECTICIDE, METHOD FOR TRACKING INHIBITING TRIPSINE SYNTHESIS COMPOUNDS, DNA PROBE, AND RNA MOLECULA. |
US6413530B1 (en) | 1999-04-21 | 2002-07-02 | University Of Florida Research Foundation, Inc. | Pesticidal peptides |
CA2370313A1 (en) | 1999-04-21 | 2000-10-26 | University Of Florida Research Foundation, Inc. | Materials and methods useful for the control of insect larvae |
-
1999
- 1999-12-08 US US09/457,509 patent/US6521664B1/en not_active Expired - Fee Related
-
2000
- 2000-11-16 AU AU17710/01A patent/AU1771001A/en not_active Abandoned
- 2000-11-16 DE DE60003466T patent/DE60003466D1/en not_active Expired - Lifetime
- 2000-11-16 AT AT00980451T patent/ATE242964T1/en not_active IP Right Cessation
- 2000-11-16 CA CA002393207A patent/CA2393207A1/en not_active Abandoned
- 2000-11-16 EP EP00980451A patent/EP1241941B1/en not_active Expired - Lifetime
- 2000-11-16 JP JP2001542730A patent/JP2004508276A/en active Pending
- 2000-11-16 WO PCT/US2000/031558 patent/WO2001041543A2/en active Search and Examination
Non-Patent Citations (1)
Title |
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See references of WO0141543A2 * |
Also Published As
Publication number | Publication date |
---|---|
ATE242964T1 (en) | 2003-07-15 |
EP1241941B1 (en) | 2003-06-18 |
WO2001041543A8 (en) | 2002-12-27 |
US6521664B1 (en) | 2003-02-18 |
WO2001041543A2 (en) | 2001-06-14 |
WO2001041543A3 (en) | 2002-01-10 |
AU1771001A (en) | 2001-06-18 |
JP2004508276A (en) | 2004-03-18 |
DE60003466D1 (en) | 2003-07-24 |
CA2393207A1 (en) | 2001-06-14 |
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